Envudeucitinib Demonstrates Sustained Efficacy and Safety in Moderate to Severe Plaque Psoriasis

Recent clinical development of envudeucitinib (previously known as ESK-001), a highly selective TYK2 inhibitor, presents promising therapeutic potential for patients with moderate to severe plaque psoriasis. Data presented at the 2025 Fall Clinical Dermatology Conference in Las Vegas, Nevada, detailed the phase 2 randomized, double-blind STRIDE study (NCT05600036), complemented by the open-label extension (OLE), which evaluated the efficacy and safety of envudeucitinib over a 52-week period, highlighting its ability to achieve and maintain treat-to-target outcomes.¹

In the 12-week placebo-controlled phase, envudeucitinib at 40 mg twice daily (BID) demonstrated rapid and significant improvements in key psoriasis measures. The study reported that by week 12, over 60% of patients treated with 40 mg twice daily achieved a Psoriasis Area and Severity Index (PASI) score of ≤1, a stringent threshold correlating with minimal disease activity, compared to less than 10% in the placebo group. Additionally, approximately 88% experienced a ≥90% PASI reduction from baseline, indicating near-complete skin clearance.^1,2

These meaningful clinical improvements continued and improved further during the extension phase. Over 52 weeks, the proportion of patients maintaining PASI ≤1 remained high, and nearly 90% achieved PASI improvements exceeding 90%. Additionally, a substantial percentage of patients achieved body surface area (BSA) involvement of ≤1% and reported minimal impact on quality of life, as measured by Dermatology Life Quality Index scores of 0 or 1. Notably, at week 52, 60% of patients on envudeucitinib 40 mg twice daily achieved BSA ≤1%, emphasizing the therapy’s potency.

"What matters to patients is how they feel and function in daily life. That is something we have measured in the long-term extension trial by using instruments such as an itch instrument and the quality of life instrument," Drappa said. "Over 60% of patients at week 52 have reported that there is really no impact anymore of psoriasis on their daily life and their functioning,” said Jörn Drappa, MD, PhD, chief medical officer at Alumis, in a statement to Dermatology Times.

The safety profile was consistent across the study duration. Adverse events primarily included mild upper respiratory infections, nasopharyngitis, headache, and COVID-19, aligning with the known safety profile of TYK2 inhibitors. No new safety signals emerged, and the tolerability observed in the controlled phase was maintained through week 52.

According to the study authors, these findings reinforce envudeucitinib’s potential as a next-generation oral agent capable of achieving treat-to-target goals in psoriasis management. Its rapid onset, sustained efficacy, and favorable safety profile suggest that envudeucitinib could fill an unmet need for patients requiring effective systemic therapy with manageable tolerability.

In clinical practice, these results support the consideration of envudeucitinib for appropriately selected patients, especially those seeking oral options that deliver rapid and durable psoriasis control. Further phase 3 studies are anticipated to confirm these promising findings and facilitate regulatory review.

“These results demonstrated sustained efficacy over time, reinforcing envudeucitinib’s potential as a differentiated next-generation oral TYK2 inhibitor,” concluded Armstrong et al.

References

1. Armstrong A, Ehst B, Hawkes J, et al. Achievement of treat-to-target thresholds with envudeucitinib, a selective tyk2 inhibitor, in moderate-to-severe plaque psoriasis: results from STRIDE and OLE. Poster presented at: 2025 Fall Clinical Dermatology Conference; October 23-26, 2025; Las Vegas, NV
2. Blauvelt A, Arenberger P, Sauder MB, et al. Highly selective, allosteric inhibition of TYK2 with oral ESK-001 in patients with moderate-to-severe plaque psoriasis: Results from STRIDE, a 12-week, randomized, double-blinded, placebo-controlled, dose-ranging phase 2 study. J Am Acad Dermatol. 2025 Jul 12:S0190-9622(25)02466-1. doi: 10.1016/j.jaad.2025.07.013